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The film is a romantic melodrama[1] about two childhood friends, Leo and Ulrich, who grow up to be soldiers in Germany. Leo becomes infatuated with Felicitas, the wife of a powerful count (a marriage about which Felicitas neglects to inform Leo). The count calls for a duel of honor with Leo, but insists that it be done under the false pretense that the quarrel was due to angry words exchanged between the two at a card game in order to protect the count's reputation. Leo kills the count in the duel, but then is punished by the military, being sent away to Africa for five years.

Due to Ulrich's intervention, Leo only serves three years before being recalled home. On his return journey he focuses on his dream of being reunited with Felicitas. Before he left for Africa, Leo had asked Ulrich to take care of Felicitas' needs while he was away. Ulrich — unaware that his friend is in love with Felicitas — falls in love with her and marries her.

Upon his return, Leo finds himself torn between Felicitas — which the woman encourages — and his friendship for Ulrich. Condemned by a local pastor for continuing to associate with Felicitas, Leo eventually loses control of his emotions, leading to a climactic duel between the two boyhood friends. While racing to stop the duel, Felicitas falls through a layer of thin ice and drowns. Meanwhile, the friends reconcile, realizing that their friendship is more important than Felicitas.

Flesh and the Devil, produced in 1926, premiered at New York's Capitol Theater[5] on January 9, 1927[6]) and marked a turning point for Garbo's personal and professional life. Initially, she refused to participate in the film. She had just finished The Temptress and was tired, plus her sister had recently died of cancer and she was upset that her contract with Metro-Goldwyn-Mayer did not allow her to take the long trip back to Sweden.[7] A sternly worded letter from MGM (read by Garbo biographer Barry Paris on the audio commentary for the 2005 DVD release of the film) warned her of dire consequences if she did not report for work. This was a rehearsal of sorts for a pitched battle Garbo would fight against studio heads after Flesh and the Devil was completed, which ended up with Garbo becoming one of the highest-paid actresses in Hollywood up to that time.

The romantic chemistry between Garbo and Gilbert was a director's dream because it was not faked. The two actors quickly became involved in their own romantic affair and before production of the film was completed had already moved in together (per Paris' commentary). Hollywood legend has it that it was also during production that Gilbert proposed to Garbo; she accepted, a high-profile wedding was arranged, but Garbo backed out. Paris disputes that this could have happened in the midst of production. Regardless of the chronology, Flesh and the Devil marked the beginning of one of the more famous romances of Hollywood's golden age. They would also continue making movies together into the Sound Era, though Gilbert's career would collapse in the early 1930s while Garbo's soared.

Garbo was so impressed with Clarence Brown's direction and William Daniels's cinematography that she continued to work with both of them in her subsequent films at MGM. She was particularly insistent on the use of Daniels as her prime cinematographer.

Flesh and the Devil was restored and released to DVD with The Temptress in September 2005 as part of a collection by Turner Classic Movies entitled Garbo Silents. The DVD includes an alternate, upbeat ending.